We propose to study the nature of the T-cell recognition structures visualized by allogeneic killer T cells and virus-restricted killer T cells. We will use in vitro mutagenesis to delete, shuffle, and mutate the exons encoding a classical transplantation antigen, the Ld molecule. These mutant forms of the Ld gene will then be transferred into mouse L cells, teratocarcinoma cells, and hopefully into normal bone marrow cells. The ability of the mutated Ld molecule to mediate T-cell killing, to interact with B2-microglobulin, and to interact with virus antigens will then be assessed to shed insights into the natures of the interactions among these molecules in the T-cell recognition structure. We also plan to study the DNA elements which control the expression of several class I genes in various cell lines and, if possible, in mice. Again the class I genes will be altered by in vitro mutagenesis and their expression assessed after appropriate gene transfer experiments.